Abstract
Interleukin-33 (IL-33) appears to play a crucial role in the expression of allergic diseases, but its cellular source and regulatory mechanisms remain to be fully elucidated. Mast cells, one of the major effecter cell populations in mediating allergy, express high levels of IL-33 receptor, ST2, and have been shown to express IL-33 transcripts. In this study, we aimed to examine the secretion of IL-33 in mast cells and their response to IL-33. We have successfully detected secreted IL-33 from cell supernatants through a modified enzyme-linked immunosorbent assay (ELISA) technique-cell-based ELISA. Activation of bone marrow-derived cultured mast cells (BMMCs) by crosslinkage of an antigen [ovalbumin (OVA)] and OVA-specific IgE mAbs significantly induced the expression of IL-33 transcripts, cytosolic and secreted proteins. In addition, the Toll-like receptor (TLR) 2 and TLR-9 ligands could trigger IL-33 mRNA expression. Exposure of BMMCs to IL-33 significantly increased the levels of IL-13 and IL-6 expression, concomitant with enhanced activation of mitogen-activated protein kinase (MAPKs) (ERK, p38, and JNK) and nuclear factor-kappa B. These results suggest that mouse BMMCs are capable of producing and serving as endogenous sources of IL-33, and that IL-33 plays an important role in regulating mast cell functions.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bone Marrow Cells / cytology
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Bone Marrow Cells / immunology*
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Cells, Cultured
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Enzyme Activation / immunology
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Enzyme-Linked Immunosorbent Assay
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Extracellular Signal-Regulated MAP Kinases / immunology
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Immunoglobulin E / immunology
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Interleukin-1 Receptor-Like 1 Protein
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Interleukin-13 / biosynthesis
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Interleukin-33
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Interleukin-6 / biosynthesis
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Interleukins / genetics
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Interleukins / immunology*
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Interleukins / metabolism
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JNK Mitogen-Activated Protein Kinases / immunology
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Mast Cells / cytology
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Mast Cells / immunology*
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Mast Cells / metabolism*
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Mice
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Mice, Inbred C57BL
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NF-kappa B / immunology
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Ovalbumin / immunology
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RNA, Messenger / genetics
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Receptors, Interleukin / biosynthesis
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Receptors, Interleukin / immunology
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Signal Transduction / immunology
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Toll-Like Receptor 2 / immunology
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Toll-Like Receptor 9 / immunology
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p38 Mitogen-Activated Protein Kinases / immunology
Substances
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Il1rl1 protein, mouse
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Il33 protein, mouse
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Interleukin-1 Receptor-Like 1 Protein
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Interleukin-13
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Interleukin-33
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Interleukin-6
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Interleukins
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NF-kappa B
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RNA, Messenger
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Receptors, Interleukin
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Tlr2 protein, mouse
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Tlr9 protein, mouse
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Toll-Like Receptor 2
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Toll-Like Receptor 9
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Immunoglobulin E
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Ovalbumin
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Extracellular Signal-Regulated MAP Kinases
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JNK Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases